Abstract 6176: CD56 dim+ immune infiltration and reprogrammed TMEs associated with response to neoadjuvant anti-PD-1 immunotherapy plus concurrent chemoradiotherapy in locally advanced gastric or gastroesophageal junction adenocarcinoma
Authors: Jia Wei, Qin Liu, Hui Chen, Xin Zhang, Feilong Zhao, Yao Fu, Ju Yang, Yue Wang, Shiqing Chen, Xiaochen Zhao, Yuezong Bai, Wenxian Guan, Baorui Liu
Journal: Cancer Research (2022)

Abstract PURPOSE Neoadjuvant immunotherapy (IO) combined with concurrent chemoradiotherapy (cCRT) showed a good efficacy in treatment of locally advanced gastric or gastroesophageal junction adenocarcinoma (G/GEJC) patients. However, the mechanism of therapeutic efficacy on tumor cells and the tumor microenvironment are still unknown. We aimed to characterize the microenvironment of immune cell infiltration at baseline and post-treatment of the patients in SHARED trial (ChiCTR1900024428). METHODS We prospectively enrolled 18 advanced G/GEJC patients who received IO (sintilimab, anti-PD-L1) in combination with cCRT therapy and resection in Nanjing Drum Tower Hospital. The pre-treatment tumor biopsies samples and post-treatment surgical specimens of all patients were measured for dynamic tumor microenvironment (TME) using mIHC (immune cell markers: CD3, CD4, CD8, FoxP3, CD20, CD56, CD68, CD163, PD-1, PD-L1) in a CLIA-certified laboratory. Twenty-five samples were successfully examined,including 10 paired pre-treatment biopsies and post-treatment specimens, three sole pre-treatment biopsies and two sole post-treatment specimens. RESULTS Among 18 patients who completed neoadjuvant treatment and resection, eight (44.4%) achieved pathological complete response (pCR), and 10 (55.6%) achieved non-pCR (six MPR and four non-MPR). Evaluable pre-treatment samples revealed a significantly higher CD56 dim+ immune infiltration (P=0.018) in pCR tumors compared with non-pCR tumors. Three patients harbored tertiary lymphoid structures (TLSs) in pre-treatment biopsies, two out of three achieved pCR and one achieved MPR. Another one patient harbored TLSs in post-treatment specimens and achieved pCR. No difference was found in all evaluable post-treatment specimens, when compared with paired pretreatment biopsies. Strikingly, significant post-treatment increases in CD3+ immune infiltration (P=0.0366) and CD4+FoxP3+ immune infiltration (P=0.0277) were observed in pCR tumors, with no significant difference in non-pCR tumors. CONCLUSIONS The different response to IO plus cCRT therapy in locally advanced G/GEJC patients and be explained by the difference in TME including the baseline CD56 dim+ immune infiltration, TLSs status and the reprogrammed immune infiltration induced by IO PLUS cCRT therapy. Further large population based studies are warranted to validate the response mechanism. Citation Format: Jia Wei, Qin Liu, Hui Chen, Xin Zhang, Feilong Zhao, Yao Fu, Ju Yang, Yue Wang, Shiqing Chen, Xiaochen Zhao, Yuezong Bai, Wenxian Guan, Baorui Liu. CD56 dim+ immune infiltration and reprogrammed TMEs associated with response to neoadjuvant anti-PD-1 immunotherapy plus concurrent chemoradiotherapy in locally advanced gastric or gastroesophageal junction adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6176.